As reported in the Journal of Clinical Oncology by Pavlakis et al, the phase III INTEGRATE IIa study showed improved overall survival with regorafenib plus best supportive care vs placebo vs best supportive care in patients with refractory advanced gastric/esophagogastric junction cancer.
Study Details
In the double-blind trial, 251 patients from sites in Asia (Korea, Taiwan, Japan; n =157) or the rest of the world (Australia, New Zealand, Canada; n = 84) who had received at least two prior therapies were randomly assigned 2:1 between October 2016 and September 2021 to receive regorafenib at 160 mg (n =169) or placebo (n = 82) once daily on days 1 to 21 of 28-day cycles until progression or unacceptable toxicity, with all patients receiving best supportive care. The primary endpoint was overall survival.
Key Findings
Median follow-up was 47 months. The regorafenib group had significantly better overall survival vs the control group (hazard ratio [HR] = 0.68, 95% confidence interval [CI] = 0.52–0.90, P = .006). Median overall survival was 4.5 months (95% CI = 4.0–5.5 months) vs 4.0 months (95% CI = 3.1–4.6 months), with 1-year rates of 19% vs 6%.
The regorafenib group had significantly better progression-free survival (HR = 0.53, 95% CI = 0.40–0.70, P < .0001). Median progression-free survival was 1.8 months (95% CI = 1.8–2.1 months) vs 1.6 months (95% CI = 1.3–1.7 months).
Grade ≥ 3 adverse events occurred in 64% of the regorafenib group vs 41% of the control group; the most common in the regorafenib group were fatigue (9%), palmar-plantar erythrodysesthesia syndrome (9%), and hypertension (8%). Serious adverse events occurred in 26% vs 16%. One treatment-related death occurred, due to hepatic failure in a patient n the regorafenib group. On the EORTC QLQ-C30, significant delay in deterioration of global quality of life was observed in the regorafenib group (HR = 0.68, 95% CI = 0.52–0.89, P = .0043).
The investigators concluded: “Regorafenib improves survival compared with placebo in refractory [advanced gastric/esophagogastric junction cancer].”
Nick Pavlakis, PhD, MBBS, FRACP, of the University of Sydney, Australia, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by an unrestricted research grant from Bayer to the Australasian Gastro-Intestinal Trials Group (AGITG); AGITG receives infrastructure funding from the Australian Government through Cancer Australia. For full disclosures of the study authors, visit ascopubs.org.
